title: Combination of external beam radiotherapy (EBRT) with intratumoral injection of dendritic cells as neo-adjuvant treatment of high-risk soft tissue sarcoma patients.
abstract: OBJECTIVE
  The goal of this study was to determine the effect of combination of intratumoral administration of dendritic cells (DC) and fractionated external beam radiation (EBRT) on tumor-specific immune responses in patients with soft-tissue sarcoma (STS).
  
  
  METHODS
  Seventeen patients with large (>5 cm) high-grade STS were enrolled in the study. They were treated in the neoadjuvant setting with 5,040 cGy of EBRT, split into 28 fractions and delivered 5 days per week, combined with intratumoral injection of 10(7) DCs followed by complete resection. DCs were injected on the second, third, and fourth Friday of the treatment cycle. Clinical evaluation and immunological assessments were performed.
  
  
  RESULTS
  The treatment was well tolerated. No patient had tumor-specific immune responses before combined EBRT/DC therapy; 9 patients (52.9%) developed tumor-specific immune responses, which lasted from 11 to 42 weeks. Twelve of 17 patients (70.6%) were progression free after 1 year. Treatment caused a dramatic accumulation of T cells in the tumor. The presence of CD4(+) T cells in the tumor positively correlated with tumor-specific immune responses that developed following combined therapy. Accumulation of myeloid-derived suppressor cells but not regulatory T cells negatively correlated with the development of tumor-specific immune responses. Experiments with (111)In labeled DCs demonstrated that these antigen presenting cells need at least 48 h to start migrating from tumor site.
  
  
  CONCLUSIONS
  Combination of intratumoral DC administration with EBRT was safe and resulted in induction of antitumor immune responses. This suggests that this therapy is promising and needs further testing in clinical trials design to assess clinical efficacy.
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA. steven.finkelstein@moffitt.org
authors.forename: Steven E
authors.initials: SE
authors.lastname: Finkelstein
authors.forename: Cristina
authors.initials: C
authors.lastname: Iclozan
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Bui
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Cotter
authors.forename: Rupal
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: Jamil
authors.initials: J
authors.lastname: Ahmed
authors.forename: David R
authors.initials: DR
authors.lastname: Noyes
authors.forename: David
authors.initials: D
authors.lastname: Cheong
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Gonzalez
authors.forename: Randy V
authors.initials: RV
authors.lastname: Heysek
authors.forename: Claudia
authors.initials: C
authors.lastname: Berman
authors.forename: Brianna C
authors.initials: BC
authors.lastname: Lenox
authors.forename: William
authors.initials: W
authors.lastname: Janssen
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Zager
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
authors.forename: G Douglas
authors.initials: GD
authors.lastname: Letson
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Antonia
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Gabrilovich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002465:Cell Movement; D003131:Combined Modality Therapy / Q000379:methods; D003713:Dendritic Cells / Q000000981:diagnostic imaging / Q000502:physiology / Q000637:transplantation*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007205:Indium Radioisotopes; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology; D015552:Injections, Intralesional; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology; D020360:Neoadjuvant Therapy / Q000379:methods; D009363:Neoplasm Proteins / Q000276:immunology; D011877:Radionuclide Imaging; D012509:Sarcoma / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: C107489:BIRC5 protein, human; D007205:Indium Radioisotopes; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D000077022:Survivin